+ Foxp3 + T Cells Affect Alveolar Bone Homeostasis via Modulating Tregs/Th17 During Induced Periodontitis: an Adoptive Transfer Experiment

摘要

Periodontitis is a dysbiotic bacteria-mediated disease characterized by periodontal inflammations and alveolar bone damage. Its mechanisms were complicated, involving an inflammation-mediated bone destruction. We sought to determine roles and rules that CD8_(+)regulatory T cells (CD8_(+)Tregs) affect alveolar bone homeostasis during periodontitis. Presence of CD8_(+)Tregs in the gingiva, cervical lymph nodes (CLNs), and spleens of healthy or periodontitis animals was analyzed. CD8_(+)regulatory T cells from periodontitis animals were sorted by magnetic-activated cell sorting and fluorescent-activated cell sorting technique, subsequently injected into recipient animals to set adoptive transfer model. We induced experimental periodontitis on transfer models and equal number healthy animals. Four weeks later, their alveolar bone loss and osteoclast coverage length were measured. We also detected CD8_(+)Tregs, CD4_(+)T cell, CD4_(+)Tregs, Th17 cell, and IL-1β, IL-6, IL-10, IL-17A, RANKL, TGF-β expression in the gingiva, CLNs, and spleen to illustrate possible working mechanism of CD8_(+)regulatory T cells. Periodontitis does not induce significant change on proportion or amount of CD8_(+)Tregs. Adoptive transfer of CD8_(+)Tregs reduces alveolar bone destruction and osteoclast formation. In addition, experimental periodontitis increases percentage of Th17 cells and decreases CD4_(+)Tregs in the gingiva and CLNs. More IL-1β, IL-6, IL-17A, and RANKL, and less IL-10 and TGF-β are also detected in the gingiva and CLNs from animals with periodontitis than the one from healthy animals. Adoptive transfer of CD8_(+)regulatory T cells remedies all above pathological change effectively. We did not find any significant difference in spleen, regardless group and detected items. Outcomes of present study clarify function that CD8_(+)regulatory T cells affect alveolar bone homeostasis, and disclose its possible working mechanisms. CD8_(+)regulatory T cells protect alveolar bone via reducing osteoclastogenesis and modulating local immune response.